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F Huppert

Publications and source records attributed to F Huppert.

11 recordsLinked to original sources
PubMed2006

Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people.

BACKGROUND: In view of the theoretical possibility of beneficial effects of DHEA or DHEAS in retarding age-associated deterioration in cognitive function, we have reviewed studies in this area. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults. SEARCH STRATEGY: Trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 October 2005 using the terms dhea*, prasterone, dehydroepiandrosterone*. In addition MEDLINE, EMBASE, PsycINFO and CINAHL were searched to find trials with volunteers who had no or minor memory complaints. Relevant journals, personal communications and conference abstracts were searched for randomized controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All randomized placebo-controlled trials enrolling people aged over 50 without dementia and to whom DHEA/S in any dosage was administered for more than one day were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (JGE and RM) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: Only three studies provided results from adequate parallel-group data. Barnhart 1999 enrolled perimenopausal women with complaints of decreased well-being and, using three cognitive measures, found no significant effect of DHEA compared with placebo at 3 months. Wolf 1998b enrolled 75 healthy volunteers (37 women and 38 men aged 59-81) in a study of the effect of DHEA supplements on cognitive impairment induced by stress; after two weeks of treatment, placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85). However, when compared with placebo, DHEA was associated with a significant impairment on a visual memory recall test (p<0.01) following the stressor. No significant effects were found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. van Niekerk 2001 found no effect on cognitive function in 46 men aged 62-76 from three months of DHEA supplementation. DHEA supplements were well tolerated and without significant adverse effects apart from the reduced performance in the visual memory recall test observed in one trial. AUTHORS' CONCLUSIONS: What little evidence there is from controlled trials does not support a beneficial effect of DHEA supplementation on cognitive function of non demented middle-aged or elderly people. There is no consistent evidence from the controlled trials that DHEA produces any adverse effects. In view of growing public enthusiasm for DHEA supplementation, particularly in the USA, and the theoretical possibility of long-term neuroprotective effects of DHEA/S, there is a need for further high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to provide adequate statistical power.

Aged↗
PubMed2002

Hormone replacement therapy for cognitive function in postmenopausal women.

BACKGROUND: As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline. OBJECTIVES: To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in randomized controlled trials (RCTs) on cognitive function in postmenopausal women. SEARCH STRATEGY: The CDCIG Specialized Register was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* on 16 May 2002. In addition MEDLINE (1966-2002/01); EMBASE (1985-2000/11); PsycINFO (1967-2002/01) and CINAHL (1982-2001/12) were searched as the CDCIG Register does not contain all trials with healthy volunteers. SELECTION CRITERIA: All double-blind randomized controlled trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the resulting lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. Two reviewers (EH and KY) assessed the quality of other aspects including design and assessment of outcomes. One reviewer (EH) extracted the data from the studies. MAIN RESULTS: In total, 15 trials involving 566 postmenopausal women were included, but 6 studies did not have adequate data for analysis. Meta-analyses showed a positive effect of 10 mg of estradiol (E2) bolus injections intramuscularly monthly in relatively young surgically menopausal women on the Paired Associate learning test immediate recall (z=2.40, p<0.05, chi-square test=1.12, p=0.29, SMD=1.02, 95% C.I.=0.19-1.85), on a test of abstract reasoning (z=10.45, p<0.0001, WMD=6.80, 95% C.I.=5.52-8.08) and a test of speed and accuracy (z=9.16, p<0.0001 WMD=6.00, 95% C.I.=4.72-7.28). However, most studies showed no evidence of an effect on verbal or visuospatial memory, mental rotations, speed or accuracy measures. There was little evidence that Premarin, the most widely prescribed estrogen for postmenopausal use, had positive effects on cognitive function. The one effect of 9 months of treatment with Premarin (and a progestagen) on a measure of complex speed of information processing (the TMT-B) was probably explained by baseline differences, as it was not reported by the authors. REVIEWER'S CONCLUSIONS: There was little evidence regarding the effect HRT or ERT on overall cognitive function in healthy postmenopausal women. There was an effect on some verbal memory functions (immediate recall), on a test of abstract reasoning and a test of speed and accuracy in relatively young (47 years of age) surgically menopausal women who had been given a bolus intramuscular injection of 10 mg E2 every month for 3 months. These effects were from small studies from a single research group. It remains to be determined whether factors such as an older age (> 69 years of age), type of menopause (surgical or natural) and type of treatment (E2 with or without a progestagen), mode of delivery (transdermal, oral or intramuscular), dosage and duration (> 3 months) could alter the effect on memory functions to a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Longitudinal RCTs currently underway in the U.S.A., U.K. and Canada will be able to test these hypotheses by the year 2010.

Cognition↗
PubMed2002

Hormone replacement therapy to maintain cognitive function in women with dementia.

BACKGROUND: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline and the development of Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The CDCIG Specialized Register, which contains up-to-date records from many medical databases was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* and Alzheim* on 16th of May 2002. In addition, MEDLINE (1966-2002/01); EMBASE (1985-2002/01); and PsyINFO (1967-2002/01) were searched. SELECTION CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane. MAIN RESULTS: A total of five trials including 210 women with AD were analysed. Meta-analyses showed that there was a limited positive effect from low dosage of conjugated equine estrogens (CEE, 0.625 mg once a day) but not from higher dosage (1.25 mg of CEE once a day) on the Mini-Mental Status Examination after 2 months (WMD=1.28, 95% C.I.=0.26 to 2.30, z=2.45, p<0.01) and the effect disappeared after 3, 6 and 12 months of treatment. This effect was small and not clinically relevant as there was only a difference of 1 point on average in comparison with the placebo users (the scale range is 0-30). There were also short-term effects of 1.25 mg of CEE on tests of concentration and executive function, namely the Trail Making Test-B (WMD=-40.90, 95% C.I.-79.29 to -2.51, z=2.09, p<0.05) and Digit Span backward (WMD=0.67, 95% C.I.=-0.01 to 1.34, z=1.94, p<0.05). With regard to memory, only cued delayed recall of a word list was positively affected by 2 months of transdermal diestradiol (E2) (WMD=6.50, 95% C.I.=4.04 to 8.96, z=5.19, p<0.0001). No HRT effects were seen on other word lists, Paragraph Recall or Paired Associate Learning. In addition, no effects were seen on visual memory, language functions, most speeded tests, clinical rating scales or depression. Controls had better performance on the delayed recall of the Paragraph Test (overall WMD=-0.45, 95% C.I.=-0.79 to -0.11, z=2.60, p<0.01) after 1 month and on Finger Tapping after 12 months (WMD=-3.90, 95% C.I.=-7.85 to 0.05, z=1.93, p<0.05). Clinicians also gave controls a better score on a dementia rating scale (CDR, overall WMD=0.35, 95% C.I.=0.01 to 0.69, z=1.99, p<0.05). Positive findings in favour of treatment or placebo could have been random effects caused by multiple analyses. After correction for multiple testing, only the short-term positive treatment effect of E2 on memory remained. REVIEWER'S CONCLUSIONS: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD. As we did not have data on women with other types of dementia (e.g. vascular dementia) this remains to be investigated. As most studies only used CEE and our earlier review in healthy women found effects only after a bolus injection of E2, it remains possible that different preparations or types of ERT or HRT could have a different effects. Several questions are raised in this review, including whether factors such as age, dementia onset (early AD), or the use of a particular preparation for a longer duration of treatment could have different effects. Perhaps the most important question is whether ERT or HRT can delay the time of onset of dementia. For answers to these questions, we have to await the results of the large RCTs currently in progress in the UK, USA, and Canada.

Cognition↗
PubMed1998

Examination of the validity of the hierarchical model of neuropathological staging in normal aging and Alzheimer's disease.

The neuropathological staging model of Alzheimer's disease proposed by Braak and Braak [Acta Neuropathol (1991) 82:259] requires that the evolution of neurofibrillary pathology follows a predictable pattern that can be ordered in a regular regional hierarchy. We have operationalized the neuropathological staging system to permit testing of its validity. Forty-two cases were derived from an epidemiological study of cognitive function in an elderly population for which post-mortem brain tissue was collected. Cases with neuropathological diagnoses other than Alzheimer's disease and normal aging were excluded. Neurofibrillary tangle counts were determined in all cortical laminae and regions used for staging. There was a significant correlation between the overall extent of neurofibrillary pathology and the number of regions affected. There were frequent order violations in the proposed hierarchy: 19 instances (45%) involving entorhinal and transentorhinal cortices, and 16 instances (38%) involving CA1 of hippocampus and entorhinal cortex. Only 6 out of 42 cases conformed in all regions to the expected hierarchy. Nevertheless, 90% of the cases had 2 order violations or less, supporting the approximate validity of the hierarchy.

Aging↗
PubMed1997

Short NART, CCRT and Spot-the-Word: comparisons in older and demented persons.

This study compares the efficacy of three measures of premorbid intelligence: the National Adult Reading Test (NART), the Cambridge Contextual Reading Test (CCRT), and the Spot-the-Word Test. The results in a population sample of elderly and demented participants show that test efficacy varies between groups. In a demented group and a normal group of average readers, the CCRT leads to a higher estimate of premorbid word reading ability than the NART. Spot-the-Word results in good performance by normal groups and participants with minimal dementia, but performance is grossly impaired in subjects with mild/moderate dementia. We conclude that each test may be appropriate for specific groups.

Aged↗
PubMed1995

Cognitive decline in an elderly population--a two wave study of change.

A sample of 1111 survivors from a population aged 75 years and over completed the Mini-Mental State Examination (MMSE) twice, separated by 28 months on average. There was a mean decline of 1.3 points in MMSE score. With increasing age, mean drop in score also increased. The proportion at each age identified as newly cognitively impaired according to any standard cut-point on MMSE rose markedly. Mean decline was greater in women than men even after adjustment for age. Cognitive change on the MMSE was approximately unimodally and normally distributed. This distribution was a marked contrast to the distribution of MMSE scores themselves, which was skewed due to truncation of scores at the maximum. The decline was not due to the inclusion of individuals with physical impairment. These findings indicate that cognitive decline, like dementia, becomes increasingly common with advancing age, and suggest that dementia may be regarded as one extreme of the continuum of cognitive decline.

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PubMed1993

Normality, deviance and minor psychiatric morbidity in the community. A population-based approach to General Health Questionnaire data in the Health and Lifestyle Survey.

This paper investigates factors affecting the distribution of psychiatric morbidity in the community. It identifies a close relationship between mean Chronic General Health Questionnaire (CGHQ) scores in subdivisions of a large random sample of the community (the Health and Lifestyle Survey, N = 6317) and the prevalence in these groups of abnormal, above-threshold CGHQ scores. The frequency distributions of CGHQ scores in these different populations move up and down as a whole: like other physiological and behavioural attributes, these mental health outcomes in individuals are associated with characteristics of the populations in which they arise. Populations thus carry a collective responsibility for their own mental health and well-being. This implies that explanations for the differing prevalence rates of psychiatric morbidity must be sought in the characteristics of their parent populations; and control measures are unlikely to succeed if they do not involve population-wide changes.

Adolescent↗
PubMed1992

The Cambridge Project for Later Life: design and preliminary results.

The Cambridge Project for Later Life is the follow-up at 2.4 years of the Hughes Hall Project for Later Life, a prevalence study of dementia in Cambridge city in which 40% of the population aged 75 and over were screened for dementia. In the follow-up, 1,173 people were screened a second time, and using Mini-Mental Scale Examination scores were selected for a more intensive interview with CAMDEX. This was followed by detailed neuropsychological testing and magnetic resonance imaging in a smaller proportion of individuals.

Aged↗